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Glucocorticoids Increase Repair Potential in a Novel in vitro Human Airway Epithelial Wounding Model

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Abstract

Airway epithelial damage is a cardinal feature of chronic asthma. Agents which enhance epithelial repair without triggering uncontrolled fibrosis of the mesenchyme would be predicted to be useful in the management of asthma. We have developed a repeat wound model using mucociliated human bronchial epithelial cell (HBEC) cultures to define the key pathways involved in airway epithelial repair, and to study the effects of potential therapeutic agents on epithelial repair in a chronic setting. We show that repair occurs primarily by cell migration to close a defect; this process requires activation of the EGF receptor (EGFR) and subsequent tyrosine kinase signalling. Migration is accompanied by up-regulation of CD44 in motile cells at the wound margins with proliferation of non-migrating cells adjacent to the wound area. In long-term studies β2 adrenoceptor agonists and phosphodiesterase (PDE) inhibitors have no effect on repair potential, in contrast chronic treatment with the glucocorticoid dexamethasone extends the lifespan of repeatedly wounded differentiated cultures. We suggest part of the beneficial effects of glucocorticoids in asthma is related to this ability to prolong repair potential following repeated episodes of epithelial injury.

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Abbreviations

ALI:

Air-liquid interface

SEM:

Scanning electron micrograph.

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ACKNOWLEDGMENTS

The G3G4 and H4C4 monoclonal antibodies developed by S. J. Kaufman and J. T. August/J. E. K. Hildreth, respectively were obtained from the Developmental Studies Hybridoma Bank (DSHB) developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. I also wish to thanks Drs Trevor Gray and Tim Self for their invaluable help with SEM and confocal imaging respectively.

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  1. Division of Therapeutics and Molecular Medicine, D floor, South Block, Queens Medical Centre, University Hospital, Nottingham, NG7 2UH, United Kingdom

    SAMUEL J. WADSWORTH, HALA S. NIJMEH & IAN P. HALL

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  1. SAMUEL J. WADSWORTH
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  2. HALA S. NIJMEH
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  3. IAN P. HALL
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Correspondence to SAMUEL J. WADSWORTH.

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WADSWORTH, S.J., NIJMEH, H.S. & HALL, I.P. Glucocorticoids Increase Repair Potential in a Novel in vitro Human Airway Epithelial Wounding Model. J Clin Immunol 26, 376–387 (2006). https://doi.org/10.1007/s10875-006-9029-z

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  • DOI: https://doi.org/10.1007/s10875-006-9029-z

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